1. Field of the Invention
The present invention relates to novel N-[(amino)alkyl]-1-pyrrolidine, 1-piperidine and 1-homopiperidinecarboxamides (and thiocarboxamides) substituted in the 2 or 3 pyrrolidine or 2, 3 or 4-piperidine and homopiperidine positions with radicals having thio, sulfinyl or sulfonyl containing linkages, their acid addition salts and hydrates, pharmaceutical methods and compositions associated therewith, and novel intermediates. The carboxamides and thiocarboxamides are useful in controlling cardiac arrhythmias in animals.
2. Information Disclosure Statement
A search of the prior art did not reveal the antiarrhythmia agents of Formula I of the present invention and the compounds are believed to be novel.
Antiarrhythmia agents having the general formula: ##STR2## are disclosed in copending U.S. application Ser. No. 345,452 filed Feb. 3, 1982. In that application, Ar is selected from naphthyl, 2,3-dihydro-1H-inden-4(or 5)yl, 2-furanyl or phenyl; R.sup.1 and R.sup.2 are selected from hydrogen, loweralkyl, cycloalkyl, phenyl or substituted phenyl, or phenyl-loweralkyl, X is oxygen or sulfur; B is thio, sulfinyl or sulfonyl; R.sup.3 and R.sup.4 are selected from hydrogen, loweralkyl, phenyl and phenyl-loweralkyl, and R.sup.3 and R.sup.4 may form a heterocyclic residue; alk.sup.1 and alk.sup.2 are straight or branched chain alkalenes (1-8 C), and pharmaceutical salts. In all of the above, phenyl may be substituted by conventional radicals. These compounds are relevant in that some might be regarded as open chain analogs of the carboxamides of the present invention.
The 1-unsubstituted pyrrolidines, piperidines and homopiperidines of Formula II, the chemical intermediates of the present invention which have the same 2, 3 or 4 positioned radicals containing thio, sulfinyl or sulfonyl linkages as those in Formula I were not found in a literature search and are believed to be novel.
The preparation of certain starting materials employed in making the novel chemical intermediates of Formula II has been reported by Kostyanovsky, R. G., et al. in Tetrahedron 30, 39-45 (1974) who prepared the L-form of 1-tosyl-2-tosyloxymethylpiperidine from L-prolinole with p-toluenesulfonyl chloride in pyridine. ##STR3## Similarly, (R)(+)-1-tosyl-2-tosyloxymethylpiperidine was prepared by Aketa, K., et al. in Chem. Pharm. Bull 24(4) 621-631 (1976) from R(+)-2-hydroxymethyl-1-tosylpiperidine and tosyl chloride in pyridine.
Methods of preparing the starting hexahydro-1H-azepin-3-ol and 4-ols, the equivalent of 3 and 4-hydroxyhomopiperidines which are precursors to the homopiperidine compounds of the invention have been disclosed in the prior art (CA 64, 17567a and CA 53, 8160g respectively).